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The ΔfbpAΔsapM candidate vaccine derived from Mycobacterium tuberculosis H37Rv is markedly immunogenic in macrophages and induces robust immunity to tuberculosis in mice.
- Source :
- Frontiers in Immunology; 2024, p1-17, 17p, 9 Graphs
- Publication Year :
- 2024
-
Abstract
- Tuberculosis (TB) remains a significant global health challenge, with approximately 1.5 million deaths per year. The Bacillus Calmette-Guérin (BCG) vaccine against TB is used in infants but shows variable protection. Here, we introduce a novel approach using a double gene knockout mutant (DKO) from wild-type Mycobacterium tuberculosis (Mtb) targeting fbpA and sapM genes. DKO exhibited enhanced anti-TB gene expression in mouse antigen-presenting cells, activating autophagy and inflammasomes. This heightened immune response improved ex vivo antigen presentation to T cells. Subcutaneous vaccination with DKO led to increased protection against TB in wild-type C57Bl/6 mice, surpassing the protection observed in caspase 1/11-deficient C57Bl/6 mice and highlighting the critical role of inflammasomes in TB protection. The DKO vaccine also generated stronger and longer-lasting protection than the BCG vaccine in C57Bl/6 mice, expanding both CD62L<superscript>-</superscript>CCR7<superscript>-</superscript>CD44<superscript>+/-</superscript>CD127<superscript>+</superscript> effector T cells and CD62L<superscript>+</superscript>CCR7<superscript>+/-</superscript>CD44<superscript>+</superscript>CD127<superscript>+</superscript> central memory T cells. These immune responses correlated with a substantial ≥ 1.7-log<subscript>10</subscript> reduction in Mtb lung burden. The DKO vaccine represents a promising new approach for TB immunization that mediates protection through autophagy and inflammasome pathways. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16643224
- Database :
- Complementary Index
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 179353700
- Full Text :
- https://doi.org/10.3389/fimmu.2024.1321657